This review by Brian J. Shayota from the University of Utah's Division of Medical Genetics provides an overview of biomarkers associated with mitochondrial diseases. Mitochondrial diseases are a diverse group of disorders characterized by neurological, muscular, and metabolic abnormalities, affecting various organ systems. The article discusses 13 biomarkers, including lactate, pyruvate, lactate:pyruvate ratio, creatine kinase, creatine, amino acid profiles, glutathione, malondialdehyde, GDF-15, FGF-21, gelsolin, neurofilament light-chain, and circulating cell-free mtDNA. Each biomarker's utility in clinical practice is evaluated based on literature reviews and studies. While most biomarkers show mixed findings, GDF-15 and FGF-21 stand out as having the greatest value, though they are not perfect. The review emphasizes the importance of understanding these biomarkers for early detection, improved patient management, and targeted therapies. The article also highlights the challenges in diagnosing mitochondrial diseases due to their variable onset and diverse clinical presentations, and suggests that molecular testing remains the standard for diagnosis, with biochemical testing playing a supplementary role.This review by Brian J. Shayota from the University of Utah's Division of Medical Genetics provides an overview of biomarkers associated with mitochondrial diseases. Mitochondrial diseases are a diverse group of disorders characterized by neurological, muscular, and metabolic abnormalities, affecting various organ systems. The article discusses 13 biomarkers, including lactate, pyruvate, lactate:pyruvate ratio, creatine kinase, creatine, amino acid profiles, glutathione, malondialdehyde, GDF-15, FGF-21, gelsolin, neurofilament light-chain, and circulating cell-free mtDNA. Each biomarker's utility in clinical practice is evaluated based on literature reviews and studies. While most biomarkers show mixed findings, GDF-15 and FGF-21 stand out as having the greatest value, though they are not perfect. The review emphasizes the importance of understanding these biomarkers for early detection, improved patient management, and targeted therapies. The article also highlights the challenges in diagnosing mitochondrial diseases due to their variable onset and diverse clinical presentations, and suggests that molecular testing remains the standard for diagnosis, with biochemical testing playing a supplementary role.